Both low density lipoproteins and very low density lipoproteins have been implicated as positive risk factors in the genesis of atherosclerosis, whereas high density lipoprotein concentration is an independent negative risk factor. Both diabetes and obesity are associated with changes in plasma lipoproteins and these changes may be related t the increased prevalence of cardiovascular disease. We are studying lipoprotein composition in obese and diabetic Pima Indians. Cholesterol and triglycerides are being measured in high density lipoprotein as well as other lipoprotein subclasses isolated by ultracentrifugation. These parameters are being compared in groups of normal and diabetic Indians with and without coronary artery disease, and the influence of therapy is being assessed. Apoprotein composition of specific lipoproteins will be measured. In addition, free fatty acid levels are being studied because of their precursor relationship to lipoproteins and their reflection of insulin action. From this study we will attempt to determine if diabetes and obesity are associated with changes in serum lipoproteins and to delineate the relation between lipoprotein levels and the pathogenesis of ischemic heart disease.